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Hofmo started her literary career submitting poems for publication to a wide variety of presses, including the communist newspaper Friheten and weekly magazines such as Hjemmet. One of her first published poems was dedicated to her close friend Ruth Maier and was published in Magasinet for Alle, opening with the lines:

“

The words, shiningly silent
I shall find
give them to you, hammer some moments together
under the frame of eternity
so you will never forget me

”

During the Holocaust, Maier was arrested, deported, and murdered in Auschwitz, and this became by all accounts the central tragedy in Hofmo's life. She was hospitalized in 1943 for depression, starting a lifelong struggle with mental illness.

Following the war, Hofmo traveled extensively and wrote essays for publication, primarily in the daily newspaper Dagbladet. The topics included travel, Nordic poetry, and philosophical topics. Among her most noted contributions are a lengthy debate on the minimal daily cost of living a life barely out of penury in Paris and a treatise in defense of her poet colleague Olav Kaste.

In 1953, she stopped publishing essays and instead concentrated on her poetry. Dagbladet published seven of her poems between 1952 and 1956. She published five poetry collections between 1946 and 1955.

She was institutionalized at Gaustad Hospital, suffering from mental illness, characterized as schizophrenia, paranoid type, from 1955 to 1971, leading to what was known as her "16 years of silence." Following her discharge, she went into a period of considerable productivity, publishing fifteen poetry collections between 1971 and 1994. From 1977 to her death she never left her apartment in the Nordstrand section of Oslo.[2][3]

Although Gunvor Hofmo and Ruth Maier both characterized their relationship as unusually close and intimate, there is no indication that it was romantic or sexual.

In 1947, Hofmo moved in with another writer, Astrid Tollefsen and became one of the first Norwegians living in an openly lesbian relationship.[4] They continued to live and travel together until Hofmo was incapacitated and committed for her mental illness.[5]

^"Astrid Tellefsen" (in Norwegian). Dagbladet. Retrieved 2008-01-24. I 1947 flyttet hun sammen med en annen kjent norsk lyriker, Gunvor Hofmo, og var en av få som på femtitallet levde i åpent lesbisk samboerskap. De bodde sammen i flere år på Tøyen i Oslo og senere på Sørlandet." - "In 1947 she moved in with another noted Norwegian poet, Gunvor Hofmo, and was one of the few who in the 50s lived in an open lesbian cohabitation arrangement. They lived together for several years at Tøyen in Oslo and later on the south coast.

^Siri Lindstad (January 2001). "En livslang kjærlighetssorg" (in Norwegian). Blikk. Archived from the original on 2008-11-21. Retrieved 2008-01-24. Å være åpen lesbisk på 50-tallet var å være en av de ytterst få. I 1947 fant Gunvor likevel en av de andre: den 25 år eldre Astrid Tollefsen, som også snart debuterte som lyriker. De bodde sammen i flere år, helt til Gunvors tvangsforestillinger tok helt overhånd" - "To be openly lesbian in the 1950s was to be among the very few. In 1947 Gunvor nevertheless found one of the others: the 25-year older Astrid Tollefsen,, who would also soon make her debut as a poet. They lived together for several years, until Gunvor's psychotic delusions completely took over.